Although the development of an effective vaccine against HIV-1 is urgent, in view of the 40 million people currently infected with the virus, no effective vaccine for this purpose has been developed yet.
In 2003, at least 18 experimental prophylactic vaccines were known to be undergoing clinical trials (Phases 1 to 3) (McMichael A J & Hanke T, Nature Medicine, 2003) and an even greater number of pre-clinical approaches attempting the preparation of an effective vaccine. Almost all of the products well known in the art use similar common approaches for preparing an immunogen. These methods include the use, in the vaccine, of integral sequences HIV-1 proteins, as recombinant proteins, recombinant DNA, or inserts in recombinant virus vectors.
Results of several vaccine trials that passed the pre-clinical stage were reported between 2003 and 2004. The Phase III trial (efficacy) of the REMUNE vaccine (combination of depleted whole inactive HIV-1 of the envelope protein), tested on over 5,000 individuals at risk of infection, failed to demonstrate protection and the trials were ended (McCarthy M, HIV Vaccine fails vaccine trial, THE LANCET, 361:755-756, 2003). In 2004, a promising candidate vaccine developed by a team from University of Oxford and University of Kenya reached the stage of Phase I/II trials but demonstrated immunogenicity in no more than one-third of tested individuals (International Conference Aids Vaccine 2004, Lausanne, Switzerland).
One of the disadvantages of the DNA vaccines, whether recombinant or from viral vectors encoding genes or whole proteins of the HIV-1, such as those already known in the state of the art, is the principle used by them, which facilitates the development of molecular escape mechanisms by the HIV-1 in response to immune and other pressures. Such a disadvantage may be one of the reasons for the failure of such vaccines. Furthermore, variation in the sequence may lead to several immunological escape mechanisms, while the immunization with T-cell epitopes from multiple viral gene products out of the context of native HIV-1 proteins can avoid recognition escape mechanisms, maintaining the induction of significative cellular immune responses (Newman M J et al, 2002).
In the specific and direct area of the development of a product, De Groot A S et al in Engineering immunogenic consensus T helper epitopes for a cross-clade HIV vaccine (2004) and in HIV vaccine development by computer assisted design: the GAIA vaccine (2005) identified conserved epitopes of the recognized HIV-1, over a large proportion of patients, by using computer-aided algorithms. The documents mentioned above also reported the insertion of said epitopes in vaccines undergoing testing at the pre-clinical stage with experimental animals. Previous reports also showed the selection of epitopes based on their ability to bind to multiple HLA molecules, with inferior results to those of De Groot A S et al, since HIV-1+ patients did not recognize said epitopes (Van den Burg S H et al, Journal of Immunology (1999), Identification of a conserved universal Th epitope in HIV-1). Wilson CC et al (Journal of Virology 2001. Identification and antigenicity of broadly cross-reactive . . . ) also use another search algorithm for sequences binding multiple HLA class II molecules, identifying a group of peptides frequently recognized by mononuclear blood cells of HIV-1+ patients.
Thus the development and testing of new formulations and combinations of epitopes remains a top priority in health research worldwide.
Among the broadly recognized challenges in obtaining effective vaccines against infections by HIV-1 (McMichael A J & Hanke T, Nature Medicine (2003)), the following are cited:                a) the construction of a vaccine capable of inducing high levels of neutralizing antibodies;        b) the construction of a vaccine capable of generating cellular immune responses (from T-lymphocyte) of greater intensity;        c) initiating new Phase III trials sooner, with an eventual combination of vaccines.        
Although anti-HIV-1 cytotoxic CD8+ T-lymphocytes effectively destroy the cells infected by the virus, their activity is fundamentally dependent on the presence of anti-HIV-1 CD4+ T-cells (Rosenberg et al, 1997; Kalams et al, 1998; Heeney et al, 2002). Therefore, the incorporation of appropriate HIV-1 epitopes recognized by the CD4+ T-cells may be essential to the success of an anti-HIV-1 vaccine candidate. However, there are only a few epitopes known for HIV-1 CD4+ T-lymphocytes, when compared to the CD8+ epitopes, which have been much more searched for.
Therefore, it is necessary to identify new epitopes of HIV-1 that are recognized by the CD4+ T-cells in the majority of individuals. These epitopes may be incorporated in an candidate vaccine based on epitopes that generate immune responses in a significant proportion of the population exposed to the virus. It is expected that this strategy, together with new strategies for the formulation of immunogens, may lead to a protective vaccine.
However, the identification of such peptides is difficult and very expensive when using the traditional methodology of overlapping peptides: hundreds or thousands of peptides synthesized step by step, with the difference of a few amino acid residues, have to be tested. Furthermore, said approach may not identify some of the epitopes in the regions between adjacent peptides, thus being cumbersome and not totally effective.
Recent literature reports have identified HIV-1 epitopes by using algorithms, as mentioned above. However, the test results have not demonstrated the expected recognition potential of the epitopes, i.e., recognized by the greatest majority of HIV-1+ patients.